Trimethylamine N-oxide (TMAO), also known by several other names and acronyms, is an organic compound with the formula (CH3)3NO. This colorless solid is usually encountered as a dihydrate. It is an oxidation product of trimethylamine and a common metabolite in animals. It is an osmolyte found in saltwater fish, sharks and rays, molluscs, and crustaceans. Along with free amino acids, it reduces the 3% salinity of seawater to about 1% of dissolved solids inside cells. TMAO decomposes to trimethylamine (TMA), which is the main odorant that is characteristic of degrading seafood. TMAO is thought to counteract the effects of urea by stabilizing protein folding in shark tissue (see Yancey 2005 J Exp Biol 208(Pt 15), p. 2819-2830; Meersman et al. 2009 Biophys J 97(9), 2559-2566).
There are enormous differences between sharks and other fish. In particular, unlike other vertebrates, sharks have a skeletal structure of cartilage instead of bone. Urea and trimethylamine in their blood and tissues help to maintain their osmotic balance. Like other sharks, the Great White's bodily fluids also contain small organic molecules. Among the most important of these from an osmotic standpoint are urea and TMAO. Both urea and TMAO are nitrogen-containing break-down products of protein metabolism. Urea is highly toxic to living tissue at moderate to high concentrations, causing proteins to de-stabilize and thus cease to function properly or at all. That is why, although a body can retain urea for a short time, it must be eventually excreted or dire physiological consequences occur. Yet sharks routinely retain bodily concentrations of urea that would kill most other vertebrates. This is largely due to the presence of even higher bodily concentrations of TMAO, which counters the protein-de-stabilizing effects of urea. Together, urea and TMAO add substantially to a shark's osmotic pressure, effectively rendering the internal fluids slightly (about 5%) “saltier” than the external environment. As a result, sharks do not need to invest any additional metabolic effort toward obtaining the water their bodies need. A constant supply of fresh water osmoses passively into a shark's body through the gills and other exposed membranes.